First Targeted Treatment for Small Cell Lung Cancer Shows Promise

VIENNA, AUSTRIA—Remarkable early results were reported from a phase 1 trial of a novel agent, rovalpituzumab tesirine (Rova-T, or S16LD6.5), in 79 patients with small cell lung cancer (SCLC) who had progressed after first- or second-line therapy. These findings were shared at the European Cancer Congress 2015 (ECC2015).

SCLC is an aggressive disease that is difficult to treat and is frequently diagnosed after it has metastasized. Five-year survival rates in SCLC, which accounts for approximately 14% of all lung cancers, are very low, at only 6%.

“While other cancers have multiple treatment options, there is only one agent approved in SCLC, and none available in the third-line setting; the outlook for these patients is dismal,” said M. Catherine Pietanza, MD, an assistant attending physician at the Memorial Sloan Kettering Cancer Center in New York, New York. Third-line therapy is given after first- and second-line treatments have failed to halt the progression of disease.

The patients ranged in age from 44 to 81 years, with a median age of 62 years. As is normal in phase I trials, they received escalating doses of Rova-T once every 3 weeks until toxicity reached a point at which the increase in dose needed to be stopped. The drug was designed to bind to DLL3 (delta-like protein 3), a protein highly expressed in approximately 70% of SCLCs.

“Of the 48 tumor samples we were able to analyze, 33 were positive for DLL3. Among the 29 DLL3+ patients we could treat at the maximum-tolerated dose of Rova-T, 10 (34%) had a partial response and nine (31%) had disease stabilization. The duration of response among these patients was more than 178 days, with no cases of disease progression,” Pietanza said.

Rova-T is an antibody drug conjugate (ADC) consisting of three components: an antibody, a linker, and the active chemotherapy, or cytotoxic payload. The antibody portion of an ADC can recognize cell surface receptors specific to and that are overexpressed in cancer cells, allowing the delivery of the chemotherapy directly to the tumor. This means the treatment is more effective, and also minimizes its exposure to normal cells, with a consequent reduction in toxicity.

“The high response rate is exciting in itself, and above that we have been able to identify a biomarker for SCLC in DLL3+, thus enabling us to target treatment in SCLC. The activity of the drug that we have seen is remarkable, and importantly, the durable, long-term responses are notable in such an aggressive disease where progression is normally very rapid,” said Pietanza.

Whereas the most common treatment for early stage NSCLC is surgery, SCLC is not usually diagnosed in time for this to be a viable option, and chemotherapy is the standard of care. The disease remains a worldwide public health problem, as it is associated with exposure to tobacco smoke and is a major cause of death from cancer. Currently, standard first-line therapy is the etoposide/platinum chemotherapy combined with radiation to the chest in limited stage disease, and second-line chemotherapy is topotecan. Because SCLC can spread quickly to the brain, patients may also undergo cranial radiation therapy.

“The first-line therapy has not changed for four decades, and there is no third-line treatment at present, so it is clear that Rova-T is likely to fulfil an unmet need for these patients. I would like to see additional, larger trials to develop it further in settings where there is a clear need in this disease. We are looking forward to further assisting in its development and to gaining a better understanding of its value in all cases of SCLC,” Pietanza concluded.